After administration of a drug in the form of eye drops or by subconjunctival injection, the concentration of the drug generally would reach, relatively with ease, therapeutically effective levels in the anterior segment of the eye including the cornea and the anterior aqueous humor. However, in tissues in the posterior segment of the eye, including the lens, the vitreous humor, the choroid and the retina, which are located in deeper sites of the eye, the concentration of a drug generally would hardly, or almost never, reach therapeutically effective levels after its topical application either in the form of eye drops or by subconjunctival injection. Therefore, for diseases of the posterior segment of the eye, there have been tried different ways for administration of drugs, such as oral administration, intravenous drip, intravitreous injection or intravitreous implant, in order to deliver the drug to tissues of the posterior segment of the eye. For example, in clinical studies of aldose reductase inhibitors for treating diabetic retinopathy and of immunosuppressant cyclosporine for treating uveitis accompanying Behcet's disease, oral route has been employed to administer those drugs. Ganciclovir, for example, which has been clinically applied as a therapeutic for cytomegalovirus infection of the uvea and the retina, has been administered by intravenous drip or in the form of an intravitreous implant. Furthermore, inhibitors of fibrosis such as triamcinolone acetonide, 5-fluorouracil and mitomycin C have been studied as therapeutics for proliferative vitreoretinopathy, by the method of direct injection into the vitreous body.
However, for oral administration, those drugs generally must be taken several times a day, which would cause a concern about the patients' poor compliance. As to intravenous drip or intravitreous injection, on the other hand, indispensable frequent visit to the doctors would be a burden on the patients. Furthermore, with intravenous drip, there is a risk of causing side effects such as renal or hepatic disorders. Direct intravitreous injection could cause intravitreous hemorrhage or could damage the retina. Intravitreous implants need a surgical operation, which would imposes a burden on the patients and present risks entailed in a surgery.
As a system for administering a drug without imposing such a burden on patients, transdermal pharmaceutical preparations of estradiol and nicotine have been on the market. However, as for pharmaceutical preparations aimed to treat diseases localized in the eye by administering a drug through the skin, there is found only a report of a pilocarpine-containing transdermal preparation, which showed an intraocular pressure lowering effect comparable to that of pilocarpine eye drops (Japanese Laid-open Patent Application H8-509716). As a drug that has been used in the form of eye drops for inducing miosis to treat a specific type of glaucoma, pilocarpine is not required to act on the posterior segment of the eye. No attempt has been known before to deliver a drug to the posterior segment of the eye by making use of percutaneous absorption of the drug.
On this background, the objective of the present invention is to provide pharmaceutical preparations for delivering a drug to the posterior segment of the eye, that can eliminate the burden on the patients of frequent visit to the doctors or of a surgical operation, and that will make it easier to achieve improved patients' compliance.